Journal of Molecular Medicine

, Volume 81, Issue 8, pp 455–470 | Cite as

Inflammatory mediators and islet β-cell failure: a link between type 1 and type 2 diabetes

  • Marc Y. Donath
  • Joachim Størling
  • Kathrin Maedler
  • Thomas Mandrup-Poulsen
Invited Review

Abstract

Pancreatic islet β-cell death occurs in type 1 and 2 diabetes mellitus, leading to absolute or relative insulin deficiency. β-cell death in type 1 diabetes is due predominantly to autoimmunity. In type 2 diabetes β-cell death occurs as the combined consequence of increased circulating glucose and saturated fatty acids together with adipocyte secreted factors and chronic activation of the innate immune system. In both diabetes types intra-islet inflammatory mediators seem to trigger a final common pathway leading to β-cell apoptosis. Therefore anti-inflammatory therapeutic approaches designed to block β-cell apoptosis could be a significant new development in type 1 and 2 diabetes.

Keywords

Apoptosis Interleukin 1 Mitogen-activated protein kinase Jun N-terminal kinase Extracellular signal-regulated kinase 

Abbreviations

DD

Death domain

ECSIT

Evolutionary conserved signaling intermediate in Toll/IL-1 pathways

ER

Endoplasmic reticulum

ERK

Extracellular signal-regulated kinase

FADD

Fas-associated death domain

FasL

Fas ligand

FFA

Free fatty acid

FLIP

Fas-associated death domain-like IL-1β converting enzyme inhibitory protein

IFN

Interferon

IKK

IκB kinase

IL

Interleukin

IL-1R1

IL-1 type 1 receptor

IL-1Ra

IL-1 receptor antagonist

iNOS

Inducible nitric oxide synthase

IRAK

IL-1R activated kinase

IRF

Interferon regulatory factor

IκB

Inhibitory κB protein

JAK

Janus tyrosine kinases

JNK

c-jun N-terminal kinase

MAP

Mitogen-activated protein

MAPK

Mitogen-activated protein kinase

MEKK

MAPK/ERK kinase kinase

MORT

Mediator of receptor induced toxicity

NF

Nuclear transcription factor

NOD

Nonobese diabetic

Pdx

Pancreatic duodenal homeobox factor

PKC

Protein kinase C

ROS

Reactive oxygen species

SAPK

Stress-activated protein kinases

SERCA

Sarco-/endoplasmic reticulum Ca2+ ATPase

STAT

Signal transducer and activator of transcription

TAK

Transforming growth factor β-activated kinase

TNF

Tumor necrosis factor

TRADD

TNF receptor associated death domain

TRAF

TNF receptor associated factor

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Marc Y. Donath
    • 1
  • Joachim Størling
    • 2
  • Kathrin Maedler
    • 1
  • Thomas Mandrup-Poulsen
    • 2
    • 3
  1. 1.Division of Endocrinology and DiabetesUniversity HospitalZurichSwitzerland
  2. 2.Steno Diabetes CenterGentofteDenmark
  3. 3.Department of Molecular Medicine, Rolf Luft Center for Diabetes ResearchKarolinska InstituteStockholmSweden

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